Bortezomib-induced hyponatremia: tolvaptan therapy permits continuation of lenalidomide, bortezomib and dexamethasone therapy in relapsed myeloma

Abstract

The development of hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) is well recognised in multiple myeloma (MM). SIADH, due to either MM or Bortezomib can be hazardous as severe hyponatremia may develop if large volumes of hypotonic intravenous fluid are used as an adjunct to chemotherapy. We report a case of Bortezomib-induced SIADH, in whom the use of tolvaptan, a vasopressin receptor-2 antagonist, permitted the continuation of triple combination anti-MM therapy with lenalidomide, Bortezomib and dexamethasone (RVD) in a female with aggressive disease, without the development of hyponatremia. Our patient had a rapid relapse, in which the use of Bortezomib as part of an RVD regimen was life-saving. The use of tolvaptan allowed continuation of therapy that is usually halted in other similarly reported cases. This case highlights the possible use of vaptans, which allows an aquaresis to occur by blocking the antidiuretic effects of vasopressin, as a treatment for Bortezomib-induced hyponatremia.

Cancer therapy-induced hyponatremia: A case-illustrated review

“…However, several recent case reports have described hyponatremia in multiple myeloma patients receiving proteasome inhibitor bortezomib therapy. 64–69 SIADH was the usual hyponatremia mechanism in these case reports. In prior phase 1 and 2 clinical trials assessing efficacy and safety of bortezomib in the treatment of multiple myeloma and other hematologic malignancies, incidence of hyponatremia ranged from 3% to 35%.…”

Hyponatraemia and the syndrome of inappropriate antidiuresis (SIAD) in cancer

“…Bortezomib, a proteosome inhibitor, used in the treatment of multiple myeloma can induce SIAD. Hyponatraemia in multiple myeloma has been successfully reversed with the AVP-receptor antagonist tolvaptan, indicating an AVP-dependent mechanism ( O’Connor-Byrne et al 2019 ). Stem cell therapy has been documented to cause SIAD, though in practice, it is difficult to tease out the effects of stem cell therapy itself, and the contribution of associated chemotherapy, such as cyclophosphamide and melphalan.…”

“…Vaptans can be useful for short-term interventions which allow i.v. fluid replacement during chemotherapy ( O’Connor-Byrne et al 2019 ) or for longer-term therapy to reverse hyponatraemic symptoms ( Bilgetekin et al 2021 ). Side effects are reflective of the aquaretic effects of the drug and include polyuria and thirst.…”